We propose to use prospectively collected dietary data to address a series of hypotheses regarding major cancers and their premalignant precursors in men and women. The cancers and precursors that we will study are those of the breast, colon and rectum, prostate, lung, kidney and bladder. Project 1 will extend the biennial follow-up of 51,529 men who completed an extensive dietary questionnaire first in 1986, and again in 1990 (The Health Professional Follow-up Study, HPFS). Follow-up to date has been nearly completed. The questionnaire has been shown to have a high degree of validity in this cohort and the between-person variation in nutrient intake is unusually wide and informative. We expect 823 incident prostate cancers, 431 cancers of the colon and rectum, and 256 lung cancers, which will provide substantial power to address dietary hypotheses. Project 2 will assess diet in relation to newly diagnosed cases of adenomatous large bowel polyps in the HPFS and among 90,000 women in the Nurses Health Study I who completed dietary questionnaires in 1980, 1984, 1986, and 1990. Strong associations between intakes of saturated fat and fiber and risk of adenomatous polyps of the colon and rectum have been observed during the early follow-up in HPFS. Project 3 will evaluate histopathologic characteristics of benign beast disease biopsies between 1991 and 1993 among 116,000 women enrolled in the Nurses Health Study II, and analyze risk in relation to dietary data to be collected in 1991. Project 4 will pool data from all major prospective studies of diet and cancer to provide detailed and precise information on dietary factors and breast cancer risk and to address dietary hypotheses in relation to renal cell and bladder cancers among women. Project 5 will be a series of methodologic studies to assess the validity and interpretation of questionnaire and biochemical indicators of dietary intake and nutritional status. Through these interrelated prospective studies, we anticipate a substantial increase in our understanding of, and thus ability to prevent, the most important cancers of men and women.